Poroelastic Modelling of CSF circulation via the incorporation of experimentally derived microscale water transport properties

We outline how multicompartmental poroelasticity is applied to the study of dementia. We utilize a 3D version of our poroelastic code to investigate the effects within parenchymal tissue. This system is coupled with multiple pipelines within the VPH-DARE@IT project which account for patient/subject-specific boundary conditions in the arterial compartment, in addition to both an image segmentation-mesh and integrated cardiovascular system model pipeline respectively. This consolidated template allows for the extraction of boundary conditions to run CFD simulations for the ventricles. Finally, we outline some experimental results that will help inform the MPET system

Detailed Analysis of Nearby Bulgelike Dwarf Stars III. Alpha and Heavy-element abundances

The present sample of nearby bulgelike dwarf stars has kinematics and metallicities characteristic of a probable inner disk or bulge origin. Ages derived by using isochrones give 10-11 Gyr for these stars and metallicities are in the range -0.80< [Fe/H]< +0.40. We calculate stellar parameters from spectroscopic data, and chemical abundances of Mg, Si, Ca, Ti, La, Ba, Y, Zr and Eu are derived by using spectrum synthesis. We found that [alpha-elements/Fe] show different patterns depending on the element. Si, Ca and Ti-to-iron ratios decline smoothly for increasing metallicities, and follow essentially the disk pattern. O and Mg, products of massive supernovae, and also the r-process element Eu, are overabundant relative to disk stars, showing a steeper decline for metallicities [Fe/H] > -0.3 dex. [s-elements/Fe] roughly track the solar values with no apparent trend with metallicity for [Fe/H] < 0, showing subsolar values for the metal rich stars. Both kinematical and chemical properties of the bulgelike stars indicate a distinct identity of this population when compared to disk stars.Comment: 21 pages, 9 figures, to appear in Ap

Till death (or an intruder) do us part: intrasexual-competition in a monogamous Primate

Polygynous animals are often highly dimorphic, and show large sex-differences in the degree of intra-sexual competition and aggression, which is associated with biased operational sex ratios (OSR). For socially monogamous, sexually monomorphic species, this relationship is less clear. Among mammals, pair-living has sometimes been assumed to imply equal OSR and low frequency, low intensity intra-sexual competition; even when high rates of intra-sexual competition and selection, in both sexes, have been theoretically predicted and described for various taxa. Owl monkeys are one of a few socially monogamous primates. Using long-term demographic and morphological data from 18 groups, we show that male and female owl monkeys experience intense intra-sexual competition and aggression from solitary floaters. Pair-mates are regularly replaced by intruding floaters (27 female and 23 male replacements in 149 group-years), with negative effects on the reproductive success of both partners. Individuals with only one partner during their life produced 25% more offspring per decade of tenure than those with two or more partners. The termination of the pair-bond is initiated by the floater, and sometimes has fatal consequences for the expelled adult. The existence of floaters and the sporadic, but intense aggression between them and residents suggest that it can be misleading to assume an equal OSR in socially monogamous species based solely on group composition. Instead, we suggest that sexual selection models must assume not equal, but flexible, context-specific, OSR in monogamous species.Wenner-Gren Foundation, L.S.B. Leakey Foundation, the National Geographic Society, National Science Foundation (BCS- 0621020), the University of Pennsylvania Research Foundation and the Zoological Society of San Diego, German Science Foundation (HU 1746-2/1

Proteolytic Processing of Nlrp1b Is Required for Inflammasome Activity

Nlrp1b is a NOD-like receptor that detects the catalytic activity of anthrax lethal toxin and subsequently co-oligomerizes into a pro-caspase-1 activation platform known as an inflammasome. Nlrp1b has two domains that promote oligomerization: a NACHT domain, which is a member of the AAA+ ATPase family, and a poorly characterized Function to Find Domain (FIIND). Here we demonstrate that proteolytic processing within the FIIND generates N-terminal and C-terminal cleavage products of Nlrp1b that remain associated in both the auto-inhibited state and in the activated state after cells have been treated with lethal toxin. Functional significance of cleavage was suggested by the finding that mutations that block processing of Nlrp1b also prevent the ability of Nlrp1b to activate pro-caspase-1. By using an uncleaved mutant of Nlrp1b, we established the importance of cleavage by inserting a heterologous TEV protease site into the FIIND and demonstrating that TEV protease processed this site and induced inflammasome activity. Proteolysis of Nlrp1b was shown to be required for the assembly of a functional inflammasome: a mutation within the FIIND that abolished cleavage had no effect on self-association of a FIIND-CARD fragment, but did reduce the recruitment of pro-caspase-1. Our work indicates that a post-translational modification enables Nlrp1b to function

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

Measurement of proton electromagnetic form factors in e+e−→ppˉe^+e^- \to p\bar{p} in the energy region 2.00-3.08 GeV

The process of $e^+e^- \rightarrow p\bar{p}$ is studied at 22 center-of-mass energy points ($\sqrt{s}$) from 2.00 to 3.08 GeV, exploiting 688.5~pb$^{-1}$ of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section~($\sigma_{p\bar{p}}$) of $e^+e^- \rightarrow p\bar{p}$ is measured with the energy-scan technique and it is found to be consistent with previously published data, but with much improved accuracy. In addition, the electromagnetic form-factor ratio ($|G_{E}/G_{M}|$) and the value of the effective ($|G_{\rm{eff}}|$), electric ($|G_E|$) and magnetic ($|G_M|$) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. $|G_{E}/G_{M}|$ and $|G_M|$ are determined with high accuracy, providing uncertainties comparable to data in the space-like region, and $|G_E|$ is measured for the first time. We reach unprecedented accuracy, and precision results in the time-like region provide information to improve our understanding of the proton inner structure and to test theoretical models which depend on non-perturbative Quantum Chromodynamics

First observations of hc→h_c \to hadrons

Based on $(4.48 \pm 0.03) \times 10^{8}$ $\psi(3686)$ events collected with the BESIII detector, five $h_c$ hadronic decays are searched for via process $\psi(3686) \to \pi^0 h_c$. Three of them, $h_c \to p \bar{p} \pi^+ \pi^-$, $\pi^+ \pi^- \pi^0$, and $2(\pi^+ \pi^-) \pi^0$ are observed for the first time, with statistical significances of 7.4$\sigma$, $4.9\sigma$, and 9.1$\sigma$, and branching fractions of $(2.89\pm0.32\pm0.55)\times10^{-3}$, $(1.60\pm0.40\pm0.32)\times10^{-3}$, and $(7.44\pm0.94\pm1.56)\times10^{-3}$, respectively, where the first uncertainties are statistical and the second systematic. No significant signal is observed for the other two decay modes, and the corresponding upper limits of the branching fractions are determined to be $B(h_c \to 3(\pi^+ \pi^-) \pi^0)<8.7\times10^{-3}$ and $B(h_c \to K^+ K^- \pi^+ \pi^-)<5.8\times10^{-4}$ at 90% confidence level.Comment: 17 pages, 16 figure

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

Measurements of Weak Decay Asymmetries of Λc+→pKS0\Lambda_c^+\to pK_S^0, Λπ+\Lambda\pi^+, Σ+π0\Sigma^+\pi^0, and Σ0π+\Sigma^0\pi^+

Using $e^+e^-\to\Lambda_c^+\bar\Lambda_c^-$ production from a 567 pb$^{-1}$ data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried out simultaneously on the four decay modes of $\Lambda_c^+\to pK_S^0$, $\Lambda \pi^+$, $\Sigma^+\pi^0$, and $\Sigma^0\pi^+$. For the first time, the $\Lambda_c^+$ transverse polarization is studied in unpolarized $e^+e^-$ collisions, where a non-zero effect is observed with a statistical significance of 2.1$\sigma$. The decay asymmetry parameters of the $\Lambda_c^+$ weak hadronic decays into $pK_S^0$, $\Lambda\pi^+$, $\Sigma^+\pi^0$ and $\Sigma^0\pi^+$ are measured to be $0.18\pm0.43(\rm{stat})\pm0.14(\rm{syst})$, $-0.80\pm0.11(\rm{stat})\pm0.02(\rm{syst})$, $-0.57\pm0.10(\rm{stat})\pm0.07(\rm{syst})$, and $-0.73\pm0.17(\rm{stat})\pm0.07(\rm{syst})$, respectively. In comparison with previous results, the measurements for the $\Lambda\pi^+$ and $\Sigma^+\pi^0$ modes are consistent but with improved precision, while the parameters for the $pK_S^0$ and $\Sigma^0\pi^+$ modes are measured for the first time

Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells

HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol